Postoperative empyema has long been suspected to prolong the survival of patients who undergo surgical resection of lung cancer. We have studied this question in a large population of lung cancer patients followed in our thoracic surgery department, and find support for the hypothesis in our clinical experience: the five year survival fraction of empyema patients is 50%. This may be the effect of nonspecific immunopotentiation by the infecting organisms, stimulating regional immune mechanisms in the field of lymphatic drainage of the resected tumor. We have worked out a safe program of non-specific stimulation of the regional lymphoid tissues for lung cancer patients using the BCG strain of Mycobacterium tuberculosis bovis. The dose of microorganisms tolerated intrapleurally has been determined in hamsters, dogs, and man, and an antibiotic regimen has been worked out which prevents systemic or local complications. Our studies in dogs and man have demonstrated that healing of the bronchial stump proceeds unimpaired despite intrapleural infection with BCG after lobectomy or pneumonectomy. With the protocol used in our pilot study project in humans, we can effect immunostimulation and prevent disability from systemic spread of the organism. We propose to study resected lung cancer patients in a randomized prospective study of intrapleural BCG therapy in the postoperative interval. We will stratify our study by cell type, preoperative clinical status, and by preoperative immunologic reactivity. Monitoring of anti tumor immunity will be accomplished using a currently effective in vitro system based on 86 Rubidium exchange as an index of tumor viability. Our pilot studies in humans indicate that the approach is safe, and results in useful new information on lung cancer, a disease which is yielding no ground to conventional modes of therapy.